Regional Node Basin Research Articles

Selective Sentinel Node Dissection in Melanoma with Trends and Future Directions

Starting with its earliest descriptions, melanoma has been recognized as a tumor with a predilection for metastasis to regional lymph nodes. This tendency led to initial recommendations for very aggressive early surgical management of the regional nodal basin. However, those recommendations were the source of much controversy over nearly a century, until the minimally invasive surgical technique of sentinel lymph node (SLN) biopsy was developed by Morton, Cochran and colleagues. This technique has been evaluated in a series of prospective clinical trials, which have clarified its role and the management of lymph nodes in this disease. Current controversies relating to SLN biopsy include optimal selection of patients for the procedure, the role of gene expression profiling in initial melanoma management, and the potential therapeutic effects of SLN biopsy-based management. In addition, the SLN appears to be a rich source of data relating to the host–tumor interface and the immune microenvironment, which may advance our understanding of the biology of melanoma. Finally, although the surgical technique is well developed at this point, there may be additional technical improvements that are possible as well.

Rate of occult metastasis in lip squamous cell carcinoma: A systematic review and meta-analysis.

The rate of occult metastasis in lip cancer is poorly studied. Management of the regional nodal basin in lip cancer is thus controversial. This study sought to understand the true rate of micrometastasis in lip cancer. Systematic review and meta-analysis was conducted of English language studies reporting lip cancer sentinel node biopsy results. Studies were obtained from the PubMed database between the years 2000 and 2023 using the search terms "sentinel node biopsy" and "squamous cell carcinoma." Random effect and fixed effect meta-analyses were performed. Thirteen studies met inclusion criteria. Low heterogeneity was noted among the studies, as indicated by the I2 inconsistency test (I2 = 0%). The rate of occult metastasis ranged between 0 and 33% (mean 9%). A total of 189 lip sentinel node biopsies had been performed. Of these, 21 revealed occult nodal metastasis (11.1%, 95% CI 7.36%-16.44%). One step, generalized linear mixed modeling revealed the true rate of occult nodal metastasis to be 10% (95% CI (0.0504, 0.1746), p < 0.0001). The rate of occult metastasis in lip cancer approaches the threshold for elective management of the regional nodal basin. Sentinel node biopsy is optimally suited for management of high-risk early T stage lip cancer.

False-negative sentinel lymph node biopsy for melanoma: a single-surgeon experience.

The status of the regional lymph node basin is of prognostic importance in patients with melanoma, making the performance of sentinel lymph node biopsies (SLNBs) a key component of patient care management, particularly with the advent of immunotherapy for adjuvant treatment. The primary goal of our study was to assess the false-negative rate of SLNBs among patients with melanoma. We conducted a retrospective review of patients with melanoma undergoing SLNB by a single surgeon between Jan. 1, 2005, and Dec. 31, 2020. We extracted and cross-referenced patient demographic and pathologic information. During the study period, 501 patients underwent an SLNB. Of these, 97 (19.4%) patients had pathologically positive sentinel lymph nodes and 404 (80.6%) patients had negative results. The latter were subject to further review; 84 (20.8%) patients subsequently developed recurrence, with 25 (6.2%) recurrences within the primary nodal basin. Isolated regional recurrence occurred in 11 (2.7%) patients and conjunction with a false-negative rate was 10.2%. Unadjusted recurrence rates were similar across each lymph node basin, including the axilla (2.7%), groin (3.6%), and neck (1.4%). The false-negative SLNB rate was 10.2% for isolated regional recurrences. These findings need to be considered in the era of using adjuvant systemic therapy for patients with melanoma.

Primary tumor site for localized Merkel cell carcinoma drives different management strategies without impacting oncologic outcomes

Background and purposeClinically localized Merkel cell carcinoma (MCC) has been associated with high rates of disease relapse. This study examines how primary tumor anatomic site drives patterns of care and outcomes in a large cohort treated in the contemporary era. Materials and methodsPatterns of care and associated outcomes were evaluated for clinically Stage I-II MCC patients treated at our institution with adjuvant radiation therapy (RT) to the primary site and/or regional nodal basin as a component of their curative intent therapy between 2014–2021. ResultsOf 80 patients who met inclusion criteria, the primary tumor anatomic site was head and neck (HN) for 42 (53%) and non-head and neck (NHN) for 38 (47%). Primary tumor risk factors were similar between cohorts. Fewer patients with HN tumors had wide local excision (WLE; HN-81% vs. NHN-100% p < 0.01). Of those undergoing WLE, patients with HN tumors received higher dose adjuvant RT (>50 Gy: HN-70% vs. NHN-8%; p < 0.01). Patients with HN tumors were less likely to undergo sentinel lymph node biopsy (HN-62%vs. NHN-100%; p < 0.01) and more likely to have elective nodal RT (HN-48% vs. NHN-0%). Despite varying management strategies, there was no significant difference in local recurrence-free survival (3-yr LRFS HN-94% vs. NHN-94%; p = 0.97), nodal recurrence-free survival (3-yr NRFS HN-89% vs. NHN-85%; p = 0.71) or overall recurrence-free survival (3-yr RFS 73% HN vs. 80% NHN; p = 0.44). ConclusionsAmong patients with primary MCC who had RT as a component of their initial treatment strategy, anatomically-driven heterogeneous treatment approaches were associated with equally excellent locoregional disease control.

Radiation, Lymph Node Dissection, or Both: Management of Lymph Node Micrometastases from Merkel Cell Carcinoma.

Regional lymph node micrometastases from Merkel cell carcinoma (MCC) can be treated with completion lymph node dissection (CLND) and/or radiation therapy (RT). It is unclear how these options compare in terms of survival benefits for patients. This retrospective cohort study used data from years 2012-2019 of the National Cancer Database. Patients with MCC and clinically negative, but pathologically positive, lymph node metastases who received RT to and/or CLND of the regional lymph node basin were included. Inverse probability weight balancing was performed using covariates followed by Cox proportional hazards modeling for survival analysis. A total of 962 patients were included [median (interquartile range) age, 74 (67-80) years, 662 (68.8%) male patients, 926 (96.3%) white patients]. The majority (63%, n=606) had a CLND only, while 18% (n=173) had RT only, and 19% (n=183) had both CLND and RT. From 2016 to 2019, usage of RT only increased from 10% to 31.8%. Multivariate analysis demonstrated that treatment modality was not associated with survival [RT versus CLND, hazard ratio (HR) 0.842, 95% confidence interval (CI) 0.621-1.142, p=0.269, RT+CLND versus CLND, HR 1.029, 95% CI 0.775-1.367, p=0.844]. This persisted after balancing weights (RT versus CLND, HR 0.837, 95% CI 0.614-1.142, p=0.262, RT+CLND versus CLND, HR 1.085, 95% CI 0.801-1.470, p=0.599). The usage of RT for nodal micrometastasis in MCC is increasing as compared with CLND. This strategy appears to be safe, with no significant difference in survival outcomes.

Tumour burden and female sex is negatively associated with health-related quality of life in melanoma patients with in-transit metastases

Background: Approximately 5% of patients with melanoma develop in-transit metastases, defined as recurrent metastases in superficial lymphatic vessels between the primary melanoma and the regional lymph node basin. Studies investigating health-related quality of life (HRQOL) in patients with melanoma have mostly combined stage III patients without considering the potential impact specifically associated with in-transit metastases on HRQOL. The aim of this study is to describe and identify factors associated with HRQOL in patients with melanoma in-transit metastases.

Trial in Progress: 2019-1001 A Phase I Study of NBTXR3 Activated by Radiotherapy for Locally Advanced or Borderline Resectable Pancreatic Ductal Adenocarcinoma (LAPC or BRPC)

<h3>Purpose/Objective(s)</h3> Patients with pancreatic ductal adenocarcinoma (PDAC), who are not eligible for surgery after induction chemotherapy often receive radiation. Although radiation therapy (RT) improves local disease control, the placement of the pancreas proves to be difficult when safely delivering therapeutic doses. NBTXR3 is a novel, potentially first-in-class radio enhancer, composed of functionalized hafnium oxide nanoparticles that is administered via one-time intratumoral injection and activated by RT. Pre-clinical testing suggests up to a 9-fold enhancement of the RT dose delivered within tumor cells. In this phase 1 trial-in-progress, the primary objective is to determine the recommended phase II dose (RP2D) of NBTXR3 for LAPC and BRPC patients undergoing RT. The secondary objectives are to evaluate the safety, feasibility, and anti-tumor response of NBTXR3 intratumoral injection on PDAC patients as well as time-to-event outcomes of subjects. <h3>Materials/Methods</h3> For the dose-finding part 1 of the study, patients with LAPC and no metastatic disease after at least 2-6 months of chemotherapy will be eligible. For part 2, the expansion at RP2D, patients with BRPC or LAPC and no metastatic disease after chemotherapy will be eligible. The statistical design of the trial uses a Bayesian optimal interval (BOIN) design. A maximum of 24 patients will be enrolled. For baseline and follow-up, imaging and blood biomarkers will be collected. Patients enrolled will receive NBTXR3, once, through intratumoral injection via endoscopic ultrasound (Day 1). Pre-treatment biopsy will be collected. Post NBTXR3 injection, blood samples will be collected at 4 time points (0,5,30, and 120 minutes). Two urine voids will be collected post injection for hafnium quantification as well. At least three days later, patients will undergo imaging for RT dosimetry and planning where NBTXR3 can be visualized. Patients will then receive 45 Gy in 15 fractions with IMRT, with regional nodal basins receiving 37.5 Gy. Follow-up period will begin 4 weeks after end of treatment and continue every 3 months for a year. Patients will be evaluated for surgery 4-12 weeks post RT. At 11-13 weeks after end of RT, if the patient is not eligible for surgery, an endoscopic ultrasound procedure will be performed. In both events, a post-treatment biopsy will be obtained. The imaging collected of pancreatic target lesion will be used to determine tumor response as per RECIST v1.1 criteria. <h3>Results</h3> Trial is open and accruing, with 8 patients enrolled so far. <h3>Conclusion</h3> We expect to determine the RP2D, safety, and preliminary efficacy of NBTXR3 in pancreatic cancer with this study with blood, tissue, and imaging correlates in 2022.

REVIEW OF THE ROLE OF BRACHYTHERAPY IN THE MANAGEMENT OF ORAL CAVITY CANCERS

From the day of invention of Radium, brachytherapy has been practised worldwide. Can any technological advancement in external beam radiotherapy replace brachytherapy? Answer probably no, especially in Gynaecological cancers as categorically stated by GEC-ESTRO experts. External beam radiation therapy using contemporary conformal techniques and brachytherapy play a signicant role in the management of oral cavity cancer. Small sized tumors in most of the oral cavity sites can be managed with brachytherapy alone either with intraoral cone or interstitial brachytherapy in order to minimize exposure of normal tissue. As these techniques do not treat regional lymph node basins, they are only appropriate to use as a single modality in selected stage I and II patients. The risk of occult nodal involvement in stage I and II is very low. External beam radiation therapy to the draining lymph node regions is used as the primary mode of irradiation when regional lymph nodes are at signicant risk for subclinical involvement, and brachytherapy may be added as a boost to the primary tumor. Since head and neck cancers are Surgeons domain, number of patients reporting to Radiation Oncology department is too low to carry out large randomized trial. Most of the patients report to Radiation Oncology department in either in late stage or in an early stage with poor general condition. This paves the way for selection bias and, of course, inferior results when compared with other modality. To evaluate the role of this therapy in treatment of head and neck cancers, we have reviewed its outcomes with oral cavity cancer. In conclusion, brachytherapy with or without EBRT can be an alternative to surgery in early and locally advanced oral cavity cancers although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner

National Practice Patterns in the Management of the Regional Lymph Node Basin After Positive Sentinel Lymph Node Biopsy for Cutaneous Melanoma.

Immediate completion lymph node dissection (CLND) for patients with sentinel lymph node (SLN) metastasis from cutaneous melanoma has been replaced largely by ultrasound nodal surveillance since the publication of two landmark trials in 2016 and 2017. National practice patterns of CLND remain poorly characterized. Patients with a diagnosis of cutaneous melanoma in 2016 and 2018 without clinical nodal disease who underwent sentinel lymph node biopsy (SLNB) were identified from the National Cancer Database (NCDB). Characteristics associated with CLND were analyzed by uni- and multivariate logistic regression. Overall survival (OS) was estimated using Kaplan-Meier and Cox proportional hazards regression analyses. Of the 3517 patients included in the study, 1405 had disease diagnosed in 2016. The patients with cutaneous melanoma diagnosed in 2016 had a median age of 60 years and a tumor thickness of 2.3 mm compared to 62 years and 2.4 mm, respectively, for the patients with cutaneous melanoma diagnosed in 2018. According to the NCDB, 40 % (n = 559) of the patients underwent CLND in 2016 compared with 6 % (n = 132) in 2018. The factors associated with receipt of CLND in 2018 included younger age (odds ratio [OR], 0.97; 95 % confidence interval [CI], 0.95-0.99; p = 0.001), rural residence (OR, 3.96; 95 % CI, 1.50-10.49; p = 0.006), head/neck tumor location (OR, 1.88; 95 % CI, 1.10-3.23; p = 0.021), and more than one positive SLN (OR, 1.80; 95 % CI, 1.17-2.76; p = 0.007). The 5-year OS did not differ between the patients who received SLNB only and those who underwent CLND (hazard ratio [HR], 0.93; p = 0.54). The rates of CLND have decreased nationally. However, patients with head/neck primary tumors who live in rural locations are more likely to undergo CLND, highlighting populations for which treatment may be non-uniform with national practice patterns.

ASO Visual Abstract: National Practice Patterns in the Management of the Regional Lymph Node Basin Following Positive Sentinel Lymph Node Biopsy for Cutaneous Melanoma.

ASO Visual Abstract: National Practice Patterns in the Management of the Regional Lymph Node Basin Following Positive Sentinel Lymph Node Biopsy for Cutaneous Melanoma.

Internal Mammary Lymph Node Biopsy during Microsurgical Breast Reconstruction: A Prospective Study.

Accurate assessment of regional lymph node basins is critical for oncological management of breast cancer. The internal mammary lymph node (IMLN) basin directly drains the medial pole of the breast, but biopsy is not commonly performed. While the axillary sentinel lymph node sample remains the standard of care, the majority of patients who have been found to have a positive IMLN biopsy have simultaneously had negative axillary sentinel lymph nodes. This study prospectively examines routine IMLN biopsy during microsurgical breast reconstruction. An IRB-approved study of routine IMLN biopsies in 270 consecutive patients who underwent microsurgical breast reconstruction was performed from July 1, 2018, to June 1, 2021. Recorded data included unilateral or bilateral breast reconstruction, unilateral or bilateral IMLN sampling, patient demographics, disease stage, and pathologic findings of IMLN. The majority of patients, 240 of 270 patients (88.9%), had bilateral reconstruction. Overall, 5 out of 270 (1.9%) patients had positive IMLN; one of these patients had positive axillary sentinel lymph nodes. The IMLN biopsy results in two of the five patients affected the clinical course as they were upstaged and required chemoradiation. Direct visualization of the internal mammary lymph nodes during dissection of the recipient vessels for microsurgical breast reconstruction allows for convenient sampling, with minimal donor site morbidity and enhances the therapeutic management of patients in whom nodal involvement is present. As such, the authors recommend IMLN sampling.

Locoregional Management and Prognostic Factors in Breast Cancer With Ipsilateral Internal Mammary and Axillary Lymph Node Involvement

Patients with breast cancer and ipsilateral axillary and internal mammary (IM) lymph node involvement (cN3b) often forgo IM node resection. Therefore, radiation is important for curative therapy. However, prognosis is not well described in the era of modern systemic therapy, and limited data exist to guide optimal locoregional treatment recommendations. We retrospectively reviewed 117 patients with nonmetastatic cN3b breast cancer treated at our institution between 2014 and 2019. Staging included ultrasound evaluation of all regional nodal basins. All patients received neoadjuvant chemotherapy, resection of the breast primary, and axillary nodal dissection, followed by adjuvant radiation to the breast/chest wall and regional nodes. Institutional guidelines recommend a 10-Gy boost to radiographically resolved nodes, and a 16-Gy boost to unresolved nodes. Overall survival, recurrence-free survival (RFS), locoregional RFS, internal mammary RFS, and distant metastasis-free survival were evaluated with Kaplan-Meier analysis. A multivariable model for RFS was constructed. Median follow-up for 117 patients was 3.82 years. Median age at diagnosis was 46 years and 56 patients (48%) were receptor group ER+/HER2-. Mastectomy was performed in 96 patients (82%), 38 (32%) had biopsy-confirmed IMC involvement, and 8 (7%) had IM node dissection. The median initial radiation dose was 50 Gy (range, 50-55 Gy) and IMC boost 10 Gy (range, 0-16 Gy). The 5-year overall survival, IM RFS, locoregional RFS, distant metastasis-free survival, and RFS were 74%, 98%, 89%, 68%, and 67%, respectively. On multivariable analysis, a clinical complete response of the IM nodes or ypN0 (pathologic complete response of nodes) status had improved 5-year RFS with hazard ratios of 0.24 (P=.006) and 0.27 (P=.05), respectively. Extranodal extension or lymphovascular invasion were associated with worse 5-year RFS with hazard ratios of 4.13 (P=.001) and 2.25 (P=.04), respectively. Multimodality therapy provides excellent locoregional control of 89% at 5 years for patients with cN3b breast cancer. Adjuvant radiation yields a 5-year IM RFS of 98%. Clinical and pathologic response of IM nodes are independently prognostic for RFS.

Management of In-Transit Metastases.

The purpose of this study is to discuss the current knowledge and future perspectives regarding the treatment options for in-transit metastases (ITM), along with the optimal algorithms for patients presenting with this adverse manifestation of melanoma. In addition to procedures historically accepted for the management of ITM, encompassing surgery and regional techniques, novel medications in the form of immune checkpoint inhibitors (ICI) and targeted therapies now represent standard options, allowing for the possibility of combined approaches, with an expanding role of systemic therapies. Melanoma in-transit metastases consist of intralymphatic neoplastic implants distributed between the primary site and the regional nodal basin, within the subepidermal and dermal lymphatics. Distinct risk factors may influence the development of ITM, and the clinical presentation can be highly heterogeneous, enhancing the complexity of the management of ITM. Surgical resection, when feasible, continues to represent a standard approach for patients with curative intent. Patients with extensive or unresectable disease may also benefit from regional approaches that include isolated limb perfusion or infusion, electrochemotherapy, and a wide variety of intralesional therapies. Over the past decade, regimens with ICI and BRAF/MEK inhibitors dramatically expanded the benefit of systemic treatments for patients with melanoma, both in the adjuvant setting and for those with advanced disease, and the combination of these modalities with regional treatments, as well as neoadjuvant approaches, may represent the future for the treatment of patients with ITM.

Prognostic Factors in Breast Cancer Patients With Clinical N3b (Ipsilateral Internal Mammary and Axillary) Disease

<h3>Purpose/Objective(s)</h3> Patients with clinical N3b (cN3b) breast cancer often do not undergo surgical resection of gross internal mammary (IM) nodes. Therefore, radiation is important for curative therapy. However, limited data exist to guide treatment recommendations. <h3>Materials/Methods</h3> We retrospectively reviewed 119 patients with non-metastatic cN3b breast cancer treated at our institution between 2014 and 2019 with curative intent. Staging included u/s evaluation of all regional nodal basins. All patients received neoadjuvant chemotherapy (NAC), surgical resection of the breast primary and nodal dissection, followed by adjuvant radiation to the chest wall/breast, infraclavicular (ICV), SCV and IM nodes. Institutional nodal boost guidelines recommend 10 Gy to radiographically resolved N3b nodal basins, and 16 Gy to unresolved N3b nodes, normal tissue constraints permitting. Patient, tumor, and treatment characteristics were collected and analyzed using a saturated multivariable analysis (MVA) model with backwards elimination to identify variables associated with improved overall survival (OS) at <i>P</i> < 0.10. Local (LC), regional control (RC), freedom from distant metastases (FFDM), and overall survival (OS) were evaluated with Kaplan Meier analysis. <h3>Results</h3> 119 patients were analyzed with a median follow-up of 2.78 years. Median age at diagnosis was 46 years, 56 (47%) were ER+/HER2-, 19 (16%) ER+/HER2+, 13 (11%) ER- /HER2+, and 31 (26%) ER-/HER2-, 86 (74%) had high grade histology, and 68 (57%) had cT3/T4 disease. Mastectomy was performed in 96 (81%) of patients, 36 (30%) had biopsy confirmed IMC involvement, and 8 (7%) had dissection of IM nodes. The median initial radiation dose was 50 Gy (range, 50-55), IMC boost 10 Gy (range, 8-16), and 41 (34%) received cumulative IMC dose > 60 Gy. The 3-year OS, FFDM, RC, and LC were 80%, 71%, 93%, and 94%, respectively. Patients with a nodal pCR of dissected nodes, had improved 3-year OS, 95% vs 71% (<i>P</i> = 0.008). Among patients who had a nodal pCR, nodal boost to > 60 Gy did not significantly improve 3-year OS, 100% vs. 93% (<i>P</i> = 0.40). In patients with less than a nodal pCR, who received IMC > 60 Gy, 3-year OS was numerically improved but was not statistically significant 81% vs. 64% (<i>P</i> = 0.33). In MVA, cumulative IMC dose > 60 Gy, nodal pCR, ER positivity, HER2 positivity, and lower clinical T-stage were independently associated with improved OS (Table 1). <h3>Conclusion</h3> Nodal pathologic response to NAC and cumulative IMC dose > 60 Gy were independently predictive for improved OS in patients with non-metastatic cN3b breast cancer treated with curative intent. Regional nodal control using a boost was excellent even among those with less than nodal pCR.

1099 Financial Implications of Implementing MSLT-II Trial Findings for Treatment of Cutaneous Malignant Melanoma Patients in A Tertiary Referral Centre in The United Kingdom

Abstract Aim Cutaneous malignant melanoma is a significant public health challenge in the United Kingdom. Since the new American Joint Committee on Cancer (AJCC) version 8 definition of melanoma staging, more melanoma patients are eligible for sentinel lymph node biopsies (SLNB). Prior to the MSLT-II trial, SLNB positive patients were treated as a distinct group within cutaneous melanoma patients and in most centres would routinely undergo lymph node clearance (LNC) of the regional lymph node basin to control disease. Given the above developments in melanoma care, we compared the cost of SLNB and monitoring to the cost of LNC for patients with melanoma. Method We retrospectively reviewed all SLNB positive patients undergoing LNC or surveillance in 2019. We measured the cost of all clinical encounters for both groups and performed a cost analysis. Results Our study shows that the mean cost per patient of axillary LNC is £4731.64 and groin LNC is £5381.78 against a cost of £2896.67 for SLNBs. Mean inpatient stay was 2.8 nights following LNC and 0.11 nights following SLNB. 50% of LNCs and 11% of SLNBs were associated with post-operative complications. Conclusions Our data shows that treating uncomplicated SLNB positive patients with surveillance rather than immediate LNC results in reduced morbidity, lower complication rate and shorter inpatient stay for the patients, as well as lower financial burden to the unit. This is reflected by the UK Consensus statement on melanoma, suggesting that LNC should not be routinely offered for positive SLNB without high-risk features.

Current Surgical Management of Inflammatory Breast Cancer.

Inflammatory breast cancer (IBC) is a rare and aggressive breast cancer characterized by erythema and edema of at least one-third of the breast. The diagnosis remains a clinical one. Standard of care involves trimodality therapy with anthracycline-based neoadjuvant chemotherapy and human epidermal growth factor receptor 2 (HER2)-directed therapy if HER2 positive, followed by modified radical mastectomy and post-mastectomy radiation therapy to the chest wall in addition to regional nodal basins including supraclavicular and internal mammary nodes. Current evidence does not support de-escalation of surgical therapy in the breast and axilla in IBC, and positive surgical margins have been associated with worse outcomes. Furthermore, sentinel node biopsy for axillary staging has a high false negative rate prohibiting its use in IBC. Delayed reconstruction is recommended for IBC due to a high recurrence rate and a potential for delay in adjuvant therapy. Contralateral prophylactic mastectomy may be considered at the time of delayed reconstruction. In this paper, we discuss available evidence and controversies in the current surgical management of patients with IBC.

The role of ultrasound examination for early identification of lymph-node metastasis of cutaneous squamous cell carcinoma: results from a single institutional center.

BACKGROUND Metastasis from cutaneous squamous cell carcinoma (cSCC) mainly involve the regional nodal basin, with an incidence ranging from 2-4% until 15% in case of high-risk tumors. When dealing with high-risk cSCC, ultrasound examination is recommended every 3-4 months during follow-up. We aimed to determine the role of US examination in the early diagnosis of nodal metastasis from cSCC. METHODS We conducted a retrospective cohort study enrolling consecutive cases of histopathologically verified cSCCs from January 2007 to March 2018. All the enrolled cases were followed for at least one year and all cases of histopathologically verified metastasis were registered. We also reported if ultrasound of the regional basin was performed between the primary diagnosis and metastasis and how the latter was identified, through ultrasounds or clinically. A Kaplan-Meier survival analysis was conducted on patients undergoing ultrasounds during follow-up. RESULTS A total of 1881 cases, belonging to 1441 patients were included. Thirty-one cases of nodal metastasis diagnosed after the primary tumor, in as many patients, were identified. All of the selected metastasis derived from high-risk primary cSCCs. Only in 19 cases ultrasound examination was performed during follow-up; of these, 10 were diagnosed through ultrasounds and 9 clinically. Survival analysis demonstrated that the time interval between primary tumor and metastasis was significantly lower for patients with metastasis diagnosed by ultrasounds than clinically (P=0.036). CONCLUSIONS Our study highlighted the need to optimize the use of nodal ultrasound examination for high-risk cSCCs in order to early detect metastasis.

Breast Cancer Skip Metastases: Frequency, Associated Tumor Characteristics, and Role of Staging Nodal Ultrasound in Detection.

BACKGROUND. Staging nodal ultrasound (US) evaluates locations beyond those assessed during routine surgical dissection and has an increasing role in breast cancer management given the growing use of neoadjuvant systemic therapy before surgical staging. OBJECTIVE. The purpose of this study is to identify the patterns of nodal spread of breast cancer observed at staging nodal US and to determine the frequency of skip metastases and associated tumor characteristics. METHODS. This retrospective study included 1269 consecutive patients (31 with bilateral synchronous cancers) who had 1300 newly diagnosed, untreated, invasive breast cancers and underwent US examination of the ipsilateral regional nodal basins from January 2016 through March 2017. Cases with suspicious nodes on US underwent fine-needle aspiration (FNA) biopsy. Cases with benign results on FNA and no suspicious nodes on US underwent sentinel lymph node biopsy. Results of US with FNA were compared with final surgical pathology. Skip metastases were defined as spread across discontiguous nodal levels or distant metastases in the absence of ipsilateral nodal metastases. The incidence and patterns of spread of skip metastases were summarized; associations with tumor characteristics were tested using the Fisher exact test. RESULTS. A total of 591 metastatic cases (45.5%) were confirmed by needle biopsy or sentinel lymph node biopsy, comprising 463 nodal metastases (N+) confirmed by FNA, 121 nodal metastases (N+) confirmed by sentinel lymph node biopsy, and seven distant organ metastases without nodal metastases (N0M1) confirmed by CT-guided biopsy. US with FNA had sensitivity of 86.0%, specificity of 100.0%, PPV of 100.0%, NPV of 89.5%, and accuracy of 93.6%. There were 34 skip metastases, for an incidence of 2.6% (34/1300) (95% CI, 1.8-3.6%) among all invasive cancers and 7.2% (34/470) (95% CI, 5.1-9.9%) among metastatic cancers detected by US and FNA. Skip metastases occurred to axillary level III (n = 4), the supraclavicular nodal basin (n = 21), the contralateral axilla (n = 2), and distant organs (n = 7). Cancers with skip metastases, compared with those with nonskip metastases, had higher rates (p = .005) of lobular histology (23.5% vs 6.7%) and mixed ductal and lobular histology (11.8% vs 6.7%). Skip metastases were not associated with grade, T category, or molecular subtype (p > .05). CONCLUSION. Skip metastases to locations beyond standard surgical axillary dissection occur in 7.2% of metastatic breast cancers. CLINICAL IMPACT. Staging nodal US identifies skip metastases that otherwise would be undetected, helping to achieve more accurate staging and minimize undertreatment.

NRG Oncology HN006: Randomized phase II/III trial of sentinel lymph node biopsy versus elective neck dissection for early-stage oral cavity cancer.

TPS6093 Background: Since patients with early-stage oral cavity cancer (OCC; T1-2N0M0; AJCC 8th ed) have a 20-30% rate of occult nodal metastases despite clinical and radiographic assessment, standard of care treatment includes elective neck dissection (END). Many patients have comprehensive surgical management of the regional cervical nodal basin even though the majority of those necks (70-80%) will not contain disease. Assessment of draining first echelon lymph nodes by sentinel lymph node (SLN) biopsy (Bx), a less invasive surgical procedure, may provide an alternative to END, while potentially reducing morbidity and cost. A decisive clinical trial comparing SLN Bx versus END can focus the HNC clinical and research community and resources on establishing the standard of care for management of the neck in early-stage OCC. Methods: In order to address the efficacy of SLN Bx in this population, we recently activated an international multi-institutional phase II/III prospective trial randomizing patients to two surgical arms: SLN Bx and END. PET/CT is an integral imaging biomarker in this trial. A node-negative PET/CT study with central read is required before randomization. Patients with a positive PET/CT central result will remain in a registry to compare imaging findings with final neck pathology. Given the current evidence available regarding morbidity for SLN Bx versus END, the phase II will determine if patient-reported neck and shoulder function and related QOL at 6 months after surgery using the Neck Dissection Impairment Index (NDII) shows a signal of superiority of SLN Bx compared to END. A total of 228 randomized patients with negative PET/CT for potential evaluation of shoulder-related morbidity with difference in 6-month NDII scores (minimum important difference ³7.5; one-sided a = 0.10; 90% power) will serve as the “Go/No-Go” decision to move forward into phase III. The phase III portion is a non-inferiority (NI) trial with disease-free survival (DFS) as the primary endpoint (NI margin hazard ratio 1.34 based on a 5% absolute difference in 2-year DFS; one-sided alpha 0.05; 80% power, and an interim look for efficacy at 67% of the events based on an O’Brien-Fleming boundary). The NDII at 6 months after surgery is a hierarchical co-primary endpoint for the phase III. Target accrual of phase III is 618 PET/CT negative patients, including those randomized in phase II (297 DFS events required for the final analysis). In addition to radiotherapy and imaging credentialing, quality assurance will include central pathology review of all negative SLN Bx cases and surgeon credentialing through an education course and SLN Bx and END case review by the surgical co-chairs. A surgical quality assurance working group will review all trial SLN Bx and END outcomes. As of 02/15/21, 7 patients have been screened and 6 of the planned 228 randomized patients in phase II have been enrolled. Clinical trial information: NCT04333537.

Solitary Liver Metastasis from Follicular Variant Papillary Thyroid Carcinoma: A Case Report

Papillary and follicular thyroid carcinomas, together known as differentiated thyroid carcinomas (DTC), are among the most curable of cancers. Distant metastases are rare events at the onset of DTC. Sites of metastases from follicular thyroid cancer (FTC) are usually osseous, and those from papillary thyroid cancer (PTC) metastasize to regional nodal basins and the lungs. Visceral metastases are rare, but the involvement of multiple sites has been reported so far. Liver metastases from differentiated thyroid carcinoma (LMDTC) are rare.We present the case of a patient with follicular variant of papillary thyroid carcinoma (FVPTC) unusually involving the liver.&#x0D; Bangladesh J. Nuclear Med. 22(2): 146-149, Jul 2019